Comparing benefits from many possible computed tomography lung cancer screening programs: Extrapolating from the National Lung Screening Trial using comparative modeling

Background: The National Lung Screening Trial (NLST) demonstrated that in current and former smokers aged 55 to 74 years, with at least 30 pack-years of cigarette smoking history and who had quit smoking no more than 15 years ago, 3 annual computed tomography (CT) screens reduced lung cancer-specific mortality by 20% relative to 3 annual chest X-ray screens. We compared the benefits achievable with 576 lung cancer screening programs that varied CT screen number and frequency, ages of screening, and eligibility based on smoking. Methods and Findings: We used five independent microsimulation models with lung cancer natural history parameters previously calibrated to the NLST to simulate life histories of the US cohort born in 1950 under all 576 programs. 'Efficient' (within model) programs prevented the greatest number of lung cancer deaths, compared to no screening, for a given number of CT screens. Among 120 'consensus efficient' (identified as efficient across models) programs, the average starting age was 55 years, the stopping age was 80 or 85 years, the average minimum pack-years was 27, and the maximum years since quitting was 20. Among consensus efficient programs, 11% to 40% of the cohort was screened, and 153 to 846 lung cancer deaths were averted per 100,000 people. In all models, annual screening based on age and smoking eligibility in NLST was not efficient; continuing screening to age 80 or 85 years was more efficient. Conclusions: Consensus results from five models identified a set of efficient screening programs that include annual CT lung cancer screening using criteria like NLST eligibility but extended to older ages. Guidelines for screening should also consider harms of screening and individual patient characteristics

Evidence for a mixed mass composition at the `ankle' in the cosmic-ray spectrum

We report a first measurement for ultra-high energy cosmic rays of the correlation between the depth of shower maximum and the signal in the water Cherenkov stations of air-showers registered simultaneously by the fluorescence and the surface detectors of the Pierre Auger Observatory. Such a correlation measurement is a unique feature of a hybrid air-shower observatory with sensitivity to both the electromagnetic and muonic components. It allows an accurate determination of the spread of primary masses in the cosmic-ray flux. Up till now, constraints on the spread of primary masses have been dominated by systematic uncertainties. The present correlation measurement is not affected by systematics in the measurement of the depth of shower maximum or the signal in the water Cherenkov stations. The analysis relies on general characteristics of air showers and is thus robust also with respect to uncertainties in hadronic event generators. The observed correlation in the energy range around the `ankle' at $\lg(E/{\rm eV})=18.5-19.0$ differs significantly from expectations for pure primary cosmic-ray compositions. A light composition made up of proton and helium only is equally inconsistent with observations. The data are explained well by a mixed composition including nuclei with mass $A > 4$. Scenarios such as the proton dip model, with almost pure compositions, are thus disfavoured as the sole explanation of the ultrahigh-energy cosmic-ray flux at Earth.Comment: Published version. Added journal reference and DOI. Added Report Numbe

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

Adjuvant treatment for melanoma in clinical practice - Trial versus reality

Background: Little is known about outcomes of adjuvant-treated melanoma patients beyond the clinical trial setting. Since 2019, adjuvant-treated melanoma patients have been registered in the DMTR, a population-based registry to monitor the quality and safety of melanoma care in the Netherlands. This study aims to describe treatment patterns, relapse, and toxicity rates of adjuvant-treated melanoma patients beyond the clinical trial setting. Methods: Analyses were performed on adjuvant-treated melanoma patients included in the DMTR. Descriptive statistics were used to analyse patient-, and treatment characteristics. A baseline registration completeness analysis was performed, and an analysis on trial eligibility in clinical practice patients. Recurrence-free survival (RFS) at 12-months was estimated with the Kaplan-Meier method. Results: A total of 641 patients were treated with adjuvant anti-PD-1 therapy. RFS at 12-months was 70.6% (95% CI, 66.9-74.6) with a median follow-up of 12.8 months. Sex, stage of disease and Breslow thickness were associated with a higher hazard for RFS. Eighteen per cent of the anti-PD-1-treated patients developed grade >= 3 toxicity. Sixty-one per cent of patients prematurely discontinued anti-PD-1 therapy. Conclusion: Adjuvant anti-PD-1 treatment of resected stage III/IV melanoma in daily practice showed slightly higher toxicity rates and more frequent premature discontinuation but similar RFS rates compared to trials. (C) 2021 The Authors. Published by Elsevier Ltd

The large trans-Neptunian object 2002 TC302 from combined stellar occultation, photometry, and astrometry data

Context. Deriving physical properties of trans-Neptunian objects is important for the understanding of our Solar System. This requires observational efforts and the development of techniques suitable for these studies. Aims. Our aim is to characterize the large trans-Neptunian object (TNO) 2002 TC302. Methods. Stellar occultations offer unique opportunities to determine key physical properties of TNOs. On 28 January 2018, 2002 TC302 occulted a mv ~ 15.3 star with designation 593-005847 in the UCAC4 stellar catalog, corresponding to Gaia source 130957813463146112. Twelve positive occultation chords were obtained from Italy, France, Slovenia, and Switzerland. Also, four negative detections were obtained near the north and south limbs. This represents the best observed stellar occultation by a TNO other than Pluto in terms of the number of chords published thus far. From the 12 chords, an accurate elliptical fit to the instantaneous projection of the body can be obtained that is compatible with the near misses. Results. The resulting ellipse has major and minor axes of 543 ± 18 km and 460 ± 11 km, respectively, with a position angle of 3 ± 1 degrees for the minor axis. This information, combined with rotational light curves obtained with the 1.5 m telescope at Sierra Nevada Observatory and the 1.23 m telescope at Calar Alto observatory, allows us to derive possible three-dimensional shapes and density estimations for the body based on hydrostatic equilibrium assumptions. The effective diameter in equivalent area is around 84 km smaller than the radiometrically derived diameter using thermal data from Herschel and Spitzer Space Telescopes. This might indicate the existence of an unresolved satellite of up to ~300 km in diameter, which is required to account for all the thermal flux, although the occultation and thermal diameters are compatible within their error bars given the considerable uncertainty of the thermal results. The existence of a potential satellite also appears to be consistent with other ground-based data presented here. From the effective occultation diameter combined with absolute magnitude measurements we derive a geometric albedo of 0.147 ± 0.005, which would be somewhat smaller if 2002 TC302 has a satellite. The best occultation light curves do not show any signs of ring features or any signatures of a global atmosphere.Funding from Spanish projects AYA2014-56637-C2-1-P, AYA2017-89637-R, from FEDER, and Proyecto de Excelencia de la Junta de Andalucía 2012-FQM1776 is acknowledged. We would like to acknowledge financial support by the Spanish grant AYA-RTI2018-098657-JI00 “LEO-SBNAF” (MCIU/AEI/FEDER, UE) and the financial support from the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award for the Instituto de Astrofísica de Andalucía (SEV- 2017-0709). Part of the research received funding from the European Union’s Horizon 2020 Research and Innovation Programme, under grant agreement no. 687378 and from the ERC programme under Grant Agreement no. 669416 Lucky Star. The following authors acknowledge the respective CNPq grants: FB-R 309578/2017-5; RV-M 304544/2017-5, 401903/2016-8; J.I.B.C. 308150/2016-3; MA 427700/2018-3, 310683/2017-3, 473002/2013-2. This study was financed in part by the Coordenação de Aperfeiaçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001 and the National Institute of Science and Technology of the e-Universe project (INCT do e-Universo, CNPq grant 465376/2014-2). GBR acknowledges CAPES-FAPERJ/PAPDRJ grant E26/203.173/2016, MA FAPERJ grant E-26/111.488/2013 and ARGJr FAPESP grant 2018/11239-8. E.F.-V. acknowledges support from the 2017 Preeminent Postdoctoral Program (P3) at UCF. C.K., R.S., A.F-T., and G.M. have been supported by the K-125015 and GINOP-2.3.2-15-2016-00003 grants of the Hungarian National Research, Development and Innovation Office (NKFIH), Hungary. G.M. was also supported by the Hungarian National Research, Development and Innovation Office (NKFIH) grant PD-128 360. R.K. and T.P. were supported by the VEGA 2/0031/18 grant

The rapid atmospheric monitoring system of the Pierre Auger Observatory

The Pierre Auger Observatory is a facility built to detect air showers produced by cosmic rays above 10(17) eV. During clear nights with a low illuminated moon fraction, the UV fluorescence light produced by air showers is recorded by optical telescopes at the Observatory. To correct the observations for variations in atmospheric conditions, atmospheric monitoring is performed at regular intervals ranging from several minutes (for cloud identification) to several hours (for aerosol conditions) to several days (for vertical profiles of temperature, pressure, and humidity). In 2009, the monitoring program was upgraded to allow for additional targeted measurements of atmospheric conditions shortly after the detection of air showers of special interest, e. g., showers produced by very high-energy cosmic rays or showers with atypical longitudinal profiles. The former events are of particular importance for the determination of the energy scale of the Observatory, and the latter are characteristic of unusual air shower physics or exotic primary particle types. The purpose of targeted (or 'rapid') monitoring is to improve the resolution of the atmospheric measurements for such events. In this paper, we report on the implementation of the rapid monitoring program and its current status. The rapid monitoring data have been analyzed and applied to the reconstruction of air showers of high interest, and indicate that the air fluorescence measurements affected by clouds and aerosols are effectively corrected using measurements from the regular atmospheric monitoring program. We find that the rapid monitoring program has potential for supporting dedicated physics analyses beyond the standard event reconstruction

The Rapid Atmospheric Monitoring System of the Pierre Auger Observatory

The Pierre Auger Observatory is a facility built to detect air showers produced by cosmic rays above 10^17 eV. During clear nights with a low illuminated moon fraction, the UV fluorescence light produced by air showers is recorded by optical telescopes at the Observatory. To correct the observations for variations in atmospheric conditions, atmospheric monitoring is performed at regular intervals ranging from several minutes (for cloud identification) to several hours (for aerosol conditions) to several days (for vertical profiles of temperature, pressure, and humidity). In 2009, the monitoring program was upgraded to allow for additional targeted measurements of atmospheric conditions shortly after the detection of air showers of special interest, e.g., showers produced by very high-energy cosmic rays or showers with atypical longitudinal profiles. The former events are of particular importance for the determination of the energy scale of the Observatory, and the latter are characteristic of unusual air shower physics or exotic primary particle types. The purpose of targeted (or "rapid") monitoring is to improve the resolution of the atmospheric measurements for such events. In this paper, we report on the implementation of the rapid monitoring program and its current status. The rapid monitoring data have been analyzed and applied to the reconstruction of air showers of high interest, and indicate that the air fluorescence measurements affected by clouds and aerosols are effectively corrected using measurements from the regular atmospheric monitoring program. We find that the rapid monitoring program has potential for supporting dedicated physics analyses beyond the standard event reconstruction

Astrophysical Interpretation Of Pierre Auger Observatory Measurements Of The Uhecr Energy Spectrum And Mass Composition

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Evidence For A Mixed Mass Composition At The ‘ankle’ In The Cosmic-ray Spectrum

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